Brown adipose tissue involution associated with progressive restriction in progenitor competence

Human brown adipose tissue (BAT) undergoes progressive involution. This involution process is not recapitulated in rodents, and the underlying mechanisms are poorly understood. Here we show that the interscapular BAT (iBAT) of rabbits whitens rapidly during early adulthood. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied by loss of brown adipogenic competence of progenitors. Single-cell RNA sequencing reveals that rabbit and human iBAT progenitors highly express the FSTL1 gene. When iBAT involutes in rabbits, adipocyte progenitors reduce FSTL1 expression and are refractory to brown adipogenic recruitment. Conversely, FSTL1 is constitutively expressed in mouse 1BAT to sustain WNT signaling and prevent involution. Progenitor incompetence and iBAT paucity can be induced in mice by genetic deletion of the Fstl1 gene or ablation of Fstl1+ progenitors. Our results highlight the hierarchy and dynamics of the BAT progenitor compartment and implicate the functional incompetence of FSTL1 -expressing progenitors in BAT involution.

Automated summary

The interscapular BAT of rabbits whitens rapidly during early adulthood, in contrast to rodents. Progenitors in rabbit and human iBAT highly express the FSTL1 gene. In rabbits, FSTL1 expression decreases in adipocyte progenitors during iBAT involution, making them refractory to brown adipogenic recruitment.